Navigation Links
Same types of cell respond differently to stimulus, Stanford study shows

STANFORD, Calif. Using new technology that allows scientists to monitor how individual cells react in the complex system of cell signaling, Stanford University researchers have uncovered a much larger spectrum of differences between each cell than ever seen before.

Cells don't all act in a uniform fashion, as was previously thought.

"Think of cells as musicians in a jazz band," said Markus Covert, PhD, assistant professor of bioengineering and senior author of the study, which will be published online in Nature June 27. Covert's lab studies complex genetic systems. "One little trumpet starts to play, and the cells go off on their own riffs. One plays off of the other."

Up to now, most of the scientific information gathered on cell signaling has been obtained from populations of cells using bulk assays due to technological limitations on the ability to examine each individual cell. The new study, using an imaging system developed at Stanford based on microfluidics, shows that scientists have been misled by the results of the cell-population-based studies.

"While the outcome of activation may be the same, the process the cells use to achieve this outcome is very different," the study authors wrote. "Population studies have not revealed the intricate network of information one observes at the single cell level."

"This really surprised us," said study co-author Stephen Quake, PhD, a professor of bioengineering at Stanford, investigator of the Howard Hughes Medical Institute and a leader in the field of microfluidics. "It sends us back to the drawing board to figure out what is really going on in cells."

Cell signaling governs basic cellular activities and coordinates cell actions in the human body. The ability of cells to correctly respond to their environments is the basis of all development, tissue repair and immunity. A better understanding of how cells talk to each other could lead to new insights into how larger biological systems operate, and possibly lead to cures for such diseases as cancer, diabetes and autoimmune disorders, which are caused by errors in this process.

"What we see is that differences between cells matter," Covert said. "Even the nuances can play a role."

To achieve his goal of studying individual cell reactions during the cell-signaling process, Covert's lab joined forces with Quake's lab.

Quake, who is also the Lee Otterson Professor in the School of Engineering, had invented the biological equivalent of the integrated circuit the microfluidic chip which enables a single researcher to achieve what once would have required dozens or more. Three years ago, researchers in his lab, Rafael Gomez-Sjoberg and Annel Leyrat, developed a microfluidic chip specifically for the study of single cells. In this study, Quake and Covert put it to use to investigate inflammatory cell signaling.

"This study is a beautiful biological application of microfluidic cell culture and really illustrates the power of the technology," Quake said.

The chip is made of three layers of a silicon-based clear elastic material and contains the microscopic equivalent of test tubes, pipettes and petri dishes. Valves and gates control fluid flow. By regulating flow, the chip carries out dozens of experiments at the same time. It's essentially a lab on a chip.

"We used a microfluidics platform that could maintain and monitor cell cultures 96 at a time," Covert said. "I was doing one at a time before that. Over a one-year period, we were able to study, with unprecedented detail, how 5,000 cells responded to signals. This took us to a totally new dimension."

The scientists put mouse fibroblast cells onto the chip and let them grow in an environmental chamber, which is mounted on an inverted microscope. The entire system, which fits on a small desktop, is computerized and provides long-term monitoring of the individual cell's response to a signal by taking pictures every few minutes.

For this study, Covert, Quake and their colleagues stimulated the cells with various concentrations of a protein that typically elicits the immune system's response to infection or cancer.

"What we found is that some cells receive the signal and activate, and some don't," said Savas Tay, PhD, a postdoctoral scholar at Stanford and at the Howard Hughes Medical Institute and co-first author of the study with graduate student Jacob Hughey. In the images, the scientists could see that the cells responded in various ways, with different timing and number of oscillations, yet their primary response, in many respects, was equal.

"Previously, we used to see the cell as a messy blob of biological material, yet there is great engineering down there," said Tay. "We needed to use mathematical modeling to understand what is going on"

"The cells were doing totally different things and we've been totally missing it," Covert said.

Added Hughey, "By observing thousands of individual cells, we were able to characterize with unprecedented detail how the cells interpret varying intensities of an external stimulus."


Contact: Tracie White
Stanford University Medical Center

Related biology news :

1. Researchers discover genetic link between both types of ALS
2. Production of biofuels could benefit by controlling the types of cells that develop in plants
3. Duffy-negative blood types no longer protected from P. Vivax malaria
4. Scientists identify common HPV genotypes in northern India, encourage vaccination
5. Molecular typesetting -- proofreading without a proofreader
6. Recruitment of reproductive features into other cell types may underlie extended lifespan in animals
7. Scientists uncover mode of action of enzyme linked with several types of cancer
8. Researchers reveal types of genes necessary for brain development
9. New technique determines the number of fat cells remains constant in all body types
10. BIO-key(R) Delivers FBI-Compliant 2 Factor Authentication Solution for First Responders
11. Men and women respond differently to stress
Post Your Comments:
(Date:6/27/2016)... June 27, 2016 Research and Markets has ... 2016-2020" report to their offering. ... America to grow at a CAGR of 12.28% during ... based on an in-depth market analysis with inputs from industry experts. ... the coming years. The report also includes a discussion of the ...
(Date:6/22/2016)... American College of Medical Genetics and Genomics was once again ... of the fastest-growing trade shows during the Fastest 50 Awards ... Las Vegas . Winners are ... of the following categories: net square feet of paid exhibit ... 2015 ACMG Annual Meeting was ranked 23 out of 50 ...
(Date:6/22/2016)... 2016   Acuant , the leading ... has partnered with RightCrowd ® to ... Management, Self-Service Kiosks and Continuous Workforce Assurance. ... functional enhancements to existing physical access control ... with an automated ID verification and authentication ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... Lemonade Stand Foundation (ALSF), a leading national childhood cancer ... bioinformatics lab, using ,big data, to advance the pace ... Liz Scott , co-executive director of ALSF and Alex,s ... Washington, D.C. , hosted by Vice President ... pediatric cancer research and awareness. The ...
(Date:6/27/2016)... , June 27, 2016  Global demand for ... percent through 2020 to $7.2 billion.  This market ... beverages, cleaning products, biofuel production, animal feed, and ... diagnostics, and biocatalysts). Food and beverages will remain ... by increasing consumption of products containing enzymes in ...
(Date:6/27/2016)... ON , June 27, 2016 /PRNewswire/ - BIOREM Inc. ... has been advised by its major shareholders, Clean Technology ... United States based venture capital ... shares of Biorem (on a fully diluted, as converted ... the disposition of their entire equity holdings in Biorem ...
(Date:6/27/2016)... SAN DIEGO , June 27, 2016  Sequenom, ... company committed to enabling healthier lives through the development ... Supreme Court of the United States ... Federal courts that the claims of Sequenom,s U.S. Patent ... the patent eligibility criteria established by the Supreme Court,s ...
Breaking Biology Technology: